Bacteria secrete nanometer-sized extracellular vesicles (EVs) into the extracellular environment for intercellular information exchange. Gram-negative bacteria-derived EVs, or outer membrane vesicles (OMVs) are spherical bilayered proteolipids, are often referred to as nanovesicles, and contain lipopolysaccharides, toxic proteins, and DNA and RNA which are nucleic acids of bacteria. Gram-positive bacteria-derived EVs also contain peptidoglycan and lipoteichoic acid, which are cell wall components of bacteria, in addition to toxic proteins and nucleic acids. According to recent studies, it has been reported that such bacteria-derived EVs play a vital role in the occurrence of inflammation diseases which have been believed to be noninfectious.
Meanwhile, it is known that around 15 million newborn babies are born each year as premature babies worldwide, and these account for a tenth or more of the number of the world's newborn babies. Such premature delivery is known to be caused by infections (urinary tract infections and vaginal infections), malformations of the uterus and uterine cervix, external fertilization, nourishment of pregnant women, and genetic factors. In addition, many researchers suggest that intrauterine infections are an important mechanism for explaining 25% to 40% of premature delivery. Pregnant women undergo anatomical, physiological and biochemical changes due to hormonal and physical changes. For example, Lactobacillus acidophilus increases, and, as a result, vaginal secretion increases and vaginal pH decreases. Thus, through pregnancy-associated microorganism studies, information on cytokine degree, pH changes, a difference in vulnerability to infection, and the like of the vagina and amniotic fluid of pregnant and non-pregnant women may be acquired.
Breast cancer is the second most cancer occurring in Korean women, and was ranked second with about 15% of an annual average number of cancer occurrence cases between 1999 and 2002. Globally, breast cancer occurs at a much higher rate in western people living in the USA, Europe, and Australia than in Asian people. Although female breast cancer in South Korea is at a much lower level than in western people, the fact that women living in a so-called westernized environment of big cities have a high incidence rate and epidemiological phenomena in which the occurrence of breast cancer tends to continuously increase compared to the past may mean that factors causing the occurrence of breast cancer are continuously inherent in the South Korean women population and are accelerating cancer occurrence. It is known that the earlier age at menarche or the later age at menopause results in the blood estrogen concentration according to a regular menstruation cycle being maintained at a higher rate, and thus a risk for breast cancer becomes higher. In addition, it is known that women with early ages at the first full term delivery have a decreased risk for breast cancer 10 years after delivery, and women with high fertility also have a low risk for breast cancer. In contrast, it is known that women having never experienced childbirth have the highest risk for breast cancer, but an accurate mechanism for effects of pregnancy on the prevention of breast cancer has not yet been discovered. Primary prevention for preventing the occurrence of breast cancer itself includes suppression of the carcinogenic environment, and changes in health behaviors and habits of individuals. For example, a method of delaying ages at menarche as late as possible by suppressing obesity or an aggressive prevention method using drugs such as hormones and the like may also be considered.
Metagenomics, also called environmental genomics, is analytics for metagenomic data obtained from samples collected from the environment. Recently, the bacterial composition of human microbiota has been listed using a method based on 16s ribosomal RNA (16s rRNA) base sequences, and 16s ribosomal RNA base sequences are analyzed using a 454FLX titanium platform. There have been studies on metagenomes analyzed in feces, vaginal secretion, and amniotic fluid of pregnant women, but there have never been studies on bacterial metagenomic analysis during pregnancy in urine because urine has been regarded as bacterial-free.
In addition, to date, there have been no cases of using bacteria-derived EVs for the induction of pregnancy or the prevention of premature delivery, and for the prevention or treatment of breast cancer.